Xu et al. conducted a multicenter, pragmatic randomized controlled trial comparing standard peripheral IV catheters (PIVCs) with long guidewire PIVCs (GW-PIVCs) in patients with difficult intravenous access (DIVA) presenting to emergency departments. The primary outcome was first-insertion success; prespecified secondary outcomes included device dwell time, device failure (all-cause), number of insertion attempts, patient and clinician satisfaction, and cost per participant. At two Australian EDs, adults meeting DIVA criteria were randomized to standard-of-care PIVCs (short or long, per usual practice) or to a 5.8-cm GW-PIVC with a retractable coiled guidewire. Ultrasound guidance was recommended in the GW-PIVC arm but discretionary in the standard-care arm: a design factor that may affect first-attempt success and requires explicit consideration in interpretation. Of 446 randomized participants (409 received a PIVC), first-attempt success was 68.0% with GW-PIVC versus 76.6% with standard PIVC (absolute difference 8.6%; OR 0.65; 95% CI 0.43–0.99; p<0.05). This corresponds to a number-needed-to-harm of approximately 12 (1 additional failed first attempt per ~12 patients) for GW-PIVC compared with standard PIVC. GW-PIVCs were more likely to be inserted by physicians or physicians-in-training (60.9% vs 39.0%), reflecting a shift in who performed the procedure. Separately, multiple insertion attempts occurred in 32.0% of GW-PIVC cases vs 22.5% of standard PIVCs (OR 1.62, 95% CI 1.06–2.48; p = 0.03). GW-PIVC was associated with a shorter median dwell time (8.3 h vs 16.2 h; mean difference −7.9 h; 95% CI −14.2 to −1.6; p=0.02), a clinically unfavorable finding. No statistically significant difference was observed in device failure or complication rates: 134.0 vs 111.8 per 1000 catheter-days; hazard ratio 1.18 (95% CI 0.72–1.95). Both patient and clinician satisfaction scores were lower in the GW-PIVC group: participant satisfaction 8/10 vs 9/10, median difference −1.00 (95% CI −1.37 to −0.63); clinician satisfaction 8/10 vs 10/10, median difference −2.00 (95% CI −2.37 to −1.63), indicating reduced acceptance of the device.